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Management of anti-HBc-positive patients with rheumatic diseases treated with disease-modifying antirheumatic drugs—a single-center analysis of 2054 patients

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Abstract

Hepatitis B virus (HBV) reactivation is a common complication of immunosuppressive treatment in high prevalence countries. Biological disease-modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than conventional immunosuppressants. The incidence of HBV reactivation during treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains open how to treat and monitor patients at risk during immunosuppressive therapy with bDMARDs. We examined 2054 patients from a German tertiary rheumatology center in order to analyze the prevalence of HBc-antibody-positivity and the incidence of HBV reactivation in German rheumatology patients treated with immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of HBV infection (anti-HBc positive). Only two patients were suffering from chronic infection (HBsAg positive). Three patients were treated pre-emptively with entecavir, and eight patients after HBV DNA reappearance. No liver failure occurred due to HBV reactivation. Compared to anti-HBc-positive patients without reactivation, the reactivation group included more patients exposed to three or more classes of bDMARDs (p = 0.017). The median HBs antibody titer was significantly lower in the reactivation group (15.0 IU/l vs. 293.5 IU/l; p = 0.001). This study shows that bDMARDs and csDMARDs can safely be administered to patients with a history of HBV, provided they are closely monitored. Low titers of anti-HBs antibodies and a history of ≥ 3 classes of immunosuppressants increase the risk of HBV reactivation. These data highlight major differences to high prevalence regions.

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Authors and Affiliations

  1. Division of Rheumatology/Immunology, University Hospital Wuerzburg, Würzburg, Germany

    Eva C. Schwaneck, Hans-Peter Tony, Ottar Gadeholt & Marc Schmalzing

  2. Institute for Hygiene and Microbiology, University of Wuerzburg, Würzburg, Germany

    Manuel Krone

  3. Division of Hepatology, University Hospital Wuerzburg, Würzburg, Germany

    Sonja Kreissl-Kemmer, Johannes Weiss & Andreas Geier

  4. Institute for Virology and Immunobiology, University of Wuerzburg, Würzburg, Germany

    Benedikt Weißbrich

Authors
  1. Eva C. Schwaneck
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  2. Manuel Krone
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  3. Sonja Kreissl-Kemmer
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  4. Benedikt Weißbrich
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  5. Johannes Weiss
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  9. Andreas Geier
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Correspondence to Eva C. Schwaneck.

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Conflict of interest

E.C. Schwaneck, H-P. Tony, O. Gadeholt, and M. Schmalzing have received travel grants, speaker’s fees, research grants, or compensation for board membership and consultancies from Celgene AbbVie, Baxalta (Shire), Chugai, Roche, Janssen, Pfizer, MSD, UCB, Novartis, and Lilly. S. Kreissl-Kemmer received a travel grant from Daiichi Sankyo. M. Krone has no competing interests. J. Weiss has received travel grants, speaker’s fees, or compensation for board membership and consultancies from AbbVie, BMS, and Gilead. A. Geier has received travel grants, speaker’s fees, research grants, or compensation for board membership and consultancies from AbbVie, BMS, Gilead, Janssen, Falk, Sequana, and Novartis. B. Weissbrich has no competing interests.

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Key messages

• Patients with low anti-HBs antibodies have a higher risk for HBV reactivation.

• Multiple successive, immunosuppressive therapies result in a high risk of HBV reactivation.

• Most patients with a history of HBV can safely receive antirheumatic therapies.

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Schwaneck, E.C., Krone, M., Kreissl-Kemmer, S. et al. Management of anti-HBc-positive patients with rheumatic diseases treated with disease-modifying antirheumatic drugs—a single-center analysis of 2054 patients. Clin Rheumatol 37, 2963–2970 (2018). https://doi.org/10.1007/s10067-018-4295-8

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  • DOI: https://doi.org/10.1007/s10067-018-4295-8

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